Asthma Risk in Infants Predicted by Total Serum Bilirubin

Total serum bilirubin levels of 9 to 11.9 mg/dL, 12 to 14.9 mg/dL, and 15 to 17.9 mg/dL were associated with an increased risk for childhood asthma, according to a retrospective study published in Pediatrics.

Patient data from the Late Impact of Getting Hyperbilirubinemia or Phototherapy study, which included a total of 109,212 infants born at ≥35 weeks’ gestation at the Kaiser Permanente Northern California hospital, were retrospectively reviewed. Before discharge, infants underwent universal bilirubin screening. In addition, clinicians also measured the infants’ total serum levels of bilirubin, using the Vitros BuBc Neonatal Bilirubin assay (Ortho Clinical Diagnostics), after the first month of birth.

Investigators included additional covariables in their assessment, including maternal age and race/ethnicity, infant sex, birth weight, gestational age, and 5-minute Apgar score. The primary outcome of interest was the incidence of asthma, defined as ≥2 outpatient asthma diagnoses and ≥2 asthma medication prescriptions within a 1-year period, separated by ≥30 days and prescribed after the age of 2 years.

The maximum levels of total serum bilirubin in 16.7% and 4.7% of infants were ≥15 mg/dL and ≥18 mg/dL, respectively. Phototherapy was administered to 11.5% of included patients. Total serum bilirubin levels of 9 to 11.9 mg/dL (hazard ratio [HR] 1.22; 95% CI, 1.11-1.34; P <.001), 12 to 14.9 mg/dL (HR, 1.18; 95% CI, 1.08-1.29; P <.001), and 15 to 17.9 mg/dL (HR, 1.30; 95% CI 1.18-1.43; P <.001) were associated with significantly greater risks for asthma in this cohort when compared with total serum bilirubin levels of 3 to 5.9 mg/L. Comparatively, a total serum bilirubin level of ≥18 mg/dL did not demonstrate an association with asthma (HR, 1.04; 95% CI, 0.90-1.20; P =.9).

The retrospective nature of the study limited the researchers’ ability to determine what the causal components associated with total serum bilirubin levels and asthma are.

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Phototherapy did not increase the risk for asthma in the propensity-adjusted analyses (HR, 1.07; 95% CI, 0.96-1.20). According to the researchers, “Because there was no dose-response relationship between maximum [total serum bilirubin] levels and asthma risk, preventing higher levels through phototherapy may not have any effect on asthma risk unless started at much lower thresholds.”


Kuzniewicz MW, Niki H, Walsh EM, McCulloch CE, Newman TB. Hyperbilirubinemia, phototherapy, and childhood asthma. Pediatrics. 2018;142(4):e20180662.